2-Alkenylamine compounds typified by allylamine have an olefin site (carbon-carbon double bond) which can be transformed into a functional group and a hetero atom (nitrogen atom), and provide building blocks useful in organic synthesis. They are therefore widely used as biologically active functional molecules, such as pharmaceuticals and agricultural chemicals, modifiers for polymers, and catalysts for chemical reactions, etc.
As a method for producing allylamines, there is known a method of reacting allyl chloride and ammonia water (Patent Literature 1). In this method, three allyl compounds, such as monoallylamine, diallylamine and triallylamine, are formed, and its side reactions (allylamine byproduct) will reduce the yield of the target product. Since the same stoichiometric amount of a salt as the product is formed, and a halogen compound is used as a raw material, it has a heavy environmental burden. In addition, in this method, an organic chlorine compound inevitably remains in the allyl compound, which produces a drawback of a poor insulating property and thus is unsuitable for use in electronics applications, for example.
In order to solve this problem, in recent years, methods of allylating amines with various transition metal catalysts that employ no halide as the allylating agent have been developed. For example, Non-patent Literature 1 reports an allylation method using a palladium catalyst in which allyl acetate is used as the allylating agent, and N,N-diformylamide is used as the substrate. However, the nucleophilicity of the amine (N,N-diformylamide) is low thereby requiring a strong base for converting into a lithium salt or a sodium salt, and the reactivity of the amine is also low thereby requiring a long time for allylation.
On the other hand, Non-patent Literature 2 describes an asymmetric allylation method using benzylamine as the substrate, and using a catalyst having palladium as the center metal, and a bidentate optically active phosphite-thioether compound as the ligand. While the amount of catalyst is small and its reactivity is high, the method requires as the solvent a halogen-based solvent placing a heavy burden on the environment, the reaction temperature must be maintained at a low level, the ligand must be separately synthesized, and catalyst preparation is cumbersome, thus rendering the industrialization of the method difficult.
Non-patent Literature 3 discloses a method for preparing allylamines using allyl carbonate as the allylating agent and a neutral rhodium complex. With trimethyl phosphite as the ligand, the reaction proceeds at room temperature in a THF solvent. However, since the amine nucleophile must be protected with toluenesulfonic acid and then must be changed to an anion using a superstoichiometric amount of a base, in order to enhance its reactivity, the reaction is essentially carried out under a strongly basic condition. The ligand and amine equivalent anion are vulnerable to oxygen and moisture, and thus the method is not suitable for large-scale synthesis.
As examples of using an iridium catalyst, methods of allylating an amine with an allylating agent, such as allyl carbonate and allyl acetate, are reported in Non-patent Literatures 4 to 6. In the methods, the yields are high, and the allylated target products can be obtained from both aliphatic amines and aromatic amines. When allyl carbonate is used as the allylating agent, decarboxylation and elimination of alcohol, such as methanol, may provide a driving force for the reaction. For large scale industrial production, the formation of gases, such as carbon dioxide, in the coproduct poses a problem in terms of safety. In addition, an expensive iridium and (chiral)phosphoramidite ligand is required as the catalyst, which is disadvantageous costwise, and depending on substrates, a stoichiometric amount of a base, such as triazabicycloundecene (TBD) or triethylamine, is required.
Methods are also known in which ruthenium is used as the center metal. Non-patent Literature 7 discloses an allylation method in which allyl carbonate is used as the allylating agent and a neutral ruthenium complex having a cyclopentadienyl anion as a complexing agent is used as the catalyst. The reaction will be complete in an hour in a THF solvent at 0° C. A highly nucleophilic piperidine is used as the amine. The feasibility of its use in other substrates is unknown.
Non-patent Literature 8 also discloses a method for producing allylamines using a dicationic ruthenium complex. By using a catalyst having a pentamethylcyclopentadienyl anion as the complexing agent, bipyridine as the ligand, and a hexafluorophosphate anion as the counter-cation, the reaction proceeds in a solvent at room temperature. These are pioneering results demonstrating the reactivity of a ruthenium complex to allylation, but in both of the references, the reactivity is low, a large amount of catalyst is required, and an allylating agent of the decarboxylation type is used, and thus it is impossible to avoid the above industrial problems.
Patent Literature 2 and Non-patent Literature 9 disclose a method for producing allylamines from allyl alcohol using a phosphoramidite ligand and an iridium catalyst. Using allyl alcohol as the allylating agent and sulfamic acid as the amine source, a primary branched allylamine can be selectively obtained. It may be mentioned as an example that first indicated a possibility of using allyl alcohol as the allylating agent, but it is accompanied by difficulties in industrialization in terms of catalyst cost and catalyst preparation.
Patent Literature 3 discloses a method for producing allyl ethers in the presence of a cyclopentadienyl ruthenium complex having an α-imino acid type ligand or an α-amino acid type ligand. According to this method, an allyl ether can be produced from an allyl alcohol and an alcohol in a dehydrating manner without using any additives. The coproduct is only water, and thus it is an environmentally friendly and very efficient method, but when applied for amines, the basicity of the substrate is believed to inhibit protonation of a ligand required for catalyst activation resulting in the loss of catalyst performance. Thus, the allylation reaction with a basic compound was thought not to proceed and its application into such a compound has not been put into practice.